Cancer Immunology, Immunotherapy

, Volume 53, Issue 7, pp 589–599 | Cite as

Identification of an antigenic peptide derived from the cancer-testis antigen NY-ESO-1 binding to a broad range of HLA-DR subtypes

  • Frank Neumann
  • Claudia Wagner
  • Boris Kubuschok
  • Stefan Stevanovic
  • Hans-Georg Rammensee
  • Michael PfreundschuhEmail author
Original Article


NY-ESO-1 is a SEREX-defined cancer-testis antigen of which several MHC I, but only few MHC II–restricted epitopes have been identified. Searching for highly promiscuous MHC II–restricted peptides that might be suitable as a CD4+ stimulating vaccine for many patients, we used the SYFPEITHI algorithm and identified an NY-ESO-1–derived pentadecamer epitope (p134–148) that induced specific CD4+ T-cell responses restricted to the HLA-DRB1 subtypes *0101, *0301, *0401, and *0701 that have a cumulative prevalence of 40% in the Caucasian population. The DR restriction of the p134–148 pentadecamer was demonstrated by inhibition with an HLA-DR antibody and a functional peptide displacement titration assay with the pan-DR-binding T-helper epitope PADRE as the competitor. The natural processing and presentation of this epitope was demonstrated by recognition of an NY-ESO-1+ melanoma cell line by T cells with specificity for p134–148. The pentadecamer p134–148 was able to induce CD4+ responses in 4/38 cancer patients tested. However, no strict correlation was found between CD4+ T-cell responses against p134–148 reactivity and anti-NY-ESO-1 antibody titers in the serum of patients, suggesting that CD4+ and B-cell responses are regulated independently. In conclusion, p134–148 holds promise as a broadly applicable peptide vaccine for patients with NY-ESO-1–positive neoplasms.


T lymphocytes Antigenic peptide epitopes MHC II Tumor immunity Vaccination 



degree Celsius


cluster of differentiation


cancer-testis antigen


dendritic cells








pan-DR-binding T-helper epitope


phosphoprotein 65


sequence-specific primer PCR


volume per volume



We thank Claudia Schormann and Evi Regitz for excellent technical assistance, as well as Elisabeth Stockert (New York Branch of the LICR) and Elke Jäger (Krankenhaus Nordwest, Frankfurt/Main, Germany) for confirming the NY-ESO-1 serology data.


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Frank Neumann
    • 1
  • Claudia Wagner
    • 1
  • Boris Kubuschok
    • 1
  • Stefan Stevanovic
    • 2
  • Hans-Georg Rammensee
    • 2
  • Michael Pfreundschuh
    • 1
    Email author
  1. 1.Med. Klinik ISaarland University Medical SchoolHomburgGermany
  2. 2.Institute for Cell Biology, Department of ImmunologyEberhard-Karls-UniversitätTübingenGermany

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